Vascular complications of ProGlide versus Prostar in transcatheter aortic valve replacement (TAVR) procedures: meta-analysis

Abstract Background The aim of this study was to compare the vascular complications of ProGlide and Prostar in percutaneous transfemoral transcatheter aortic valve replacement. Methods Electronic databases were searched in July 2022 for studies that compared the vascular complications of ProGlide and Prostar for percutaneous closure in transcatheter aortic valve replacement. The primary outcome was major vascular complications and the secondary outcomes were minor vascular complications, types of access-site vascular complications, device failure, and additional intervention. Estimates of relative effects were pooled to generate ORs and their 95 per cent c.i. using a random-effects model. The risk of bias in non-randomized comparative studies was assessed using the Risk Of Bias In Non-randomized Studies - of Interventions (‘ROBINS-I’) tool. Results Nine studies were identified and a total of 7529 patients were included. Among them, 4144 patients received ProGlide and 3385 received Prostar. The pooled data showed that the risk of major vascular complications was significantly lower with ProGlide versus Prostar (OR 0.50, 95 per cent c.i. 0.32 to 0.78). Regarding the types of vascular complications, vascular trauma was the most common complication and the risk was similar between groups (OR 1.02, 95 per cent c.i. 0.55 to 1.91). ProGlide had a lower risk of bleeding complications (OR 0.46, 95 per cent c.i. 0.22 to 0.94), but a higher risk of ischaemia complications (OR 1.90, 95 per cent c.i. 1.10 to 3.27). The risk of device failure was lower in the ProGlide group (OR 0.45, 95 per cent c.i. 0.21 to 0.95). Both groups had a similar risk of having additional interventions for vascular complications (OR 1.02, 95 per cent c.i. 0.75 to 1.39). The use of ProGlide was associated with a lower risk of additional surgical treatments (OR 0.52, 95 per cent c.i. 0.34 to 0.80), but a higher risk of endovascular treatments (OR 2.69, 95 per cent c.i. 1.29 to 5.63). Conclusion In percutaneous transfemoral transcatheter aortic valve replacement procedures, ProGlide has superior safety and efficacy when compared with Prostar; it is associated with fewer major vascular complications and device failures. The vascular complications of ProGlide are more likely to be dealt with using endovascular treatments than surgical treatments.


Introduction
In the past few decades, transcatheter aortic valve replacement (TAVR) with large-bore transfemoral access has been widely performed due to its superior outcomes compared with alternative access 1,2 . Compared with surgical cut down of the femoral artery, percutaneous transfemoral TAVR with vascular closure devices (VCDs) has fewer vascular complications 3 . In TAVR patients, major vascular complications are independently associated with 1-year mortality 4,5 . Therefore, it is important to determine the optimal VCD that results in the fewest vascular complications in TAVR with large-bore transfemoral access.
There are several types of commercially available VCDs for large-bore arteriotomy with considerable rates of success and acceptable rates of vascular complications 6 . Among them, the most commonly used VCDs are two suture-based systems: Perclose ProGlide and Prostar XL (both by Abbott Vascular, Plymouth, MN, USA). Comparisons between ProGlide and Prostar have been reported in several studies; however, the results are inconsistent 7,8 . Currently, there is no clear evidence regarding which suture-based VCD is optimal in terms of vascular complications, and the selection of VCD is mainly based on the preference of the surgeon.
Previously, one systematic review conducted in 2017 compared ProGlide and Prostar for procedures with large-bore transfemoral access, and no significant differences were observed in the rate of vascular complications 9 . In the past 5 years, more research evidence has been published, with the results being inconsistent with the previous review. With more available data, the aim of the current systematic review and meta-analysis was to compare the difference in vascular complications between ProGlide and Prostar in transfemoral TAVR.

Search strategy
This systematic review and meta-analysis was registered in the PROSPERO system (No. CRD42022290571) and conducted in accordance with the PRISMA guidelines 10 . Electronic databases, including Embase, PubMed, and the Cochrane Library, were searched for eligible articles in July 2022. The search strategy used the terms 'Prostar', 'ProGlide', 'Perclose', 'suture based', 'vascular closure', 'artery closure', 'arteriotomy closure', 'aortic valve replacement', and 'aortic valve implantation'. Free-text words were used in combination with the Boolean operators 'AND' or 'OR'. The search was limited to papers written in English, and the reference lists of eligible articles were further searched. The detailed search strategy can be found in Table S1.

Study selection and data collection
Articles comparing the procedural vascular complications of two suture-based VCDs in TAVR with large-bore transfemoral access were eligible, including retrospective or prospective observational studies and RCTs. Studies reporting the outcome of a clip VCD, a collagen-based VCD, a gel-based VCD, or only one type of suture-based VCD were excluded. Reviews, letters, editorial materials, studies reporting duplicated populations, and studies without enough data were also excluded.
The titles and abstracts of the articles were independently screened by two authors (Y.X. and C.C.), and the full-length potential eligible articles were reviewed. The data of eligible articles were collected independently by two authors (Y.X. and C.C.), and the matched data in the observational studies were collected if available. Details regarding the study characteristics, patient characteristics, transfemoral sheath size, vascular complications, device failure, and additional intervention were independently collected and recorded in the predetermined data collection form by two authors (Y.X. and C.C.). Disagreements were resolved by consensus after discussion between the two authors or consultation with a third author (B.H.).
The primary outcome was major vascular complications, which were defined according to the Valve Academic Research Consortium (VARC) 11,12 . The secondary outcomes were minor vascular complications, types of access-site vascular complications, device failure, and additional intervention. Minor vascular complications were also defined according to the VARC. The types of access-site vascular complications consisted of vascular trauma (dissection, pseudoaneurysm, fistula, rupture, or perforation), bleeding (access-site bleeding or haematoma), and ischaemia (stenosis, occlusion, or embolism). Device failure was defined as the inability to achieve haemostasis at the arteriotomy site, leading to alternative treatments. Additional interventions were defined as procedures performed for vascular complications when necessary, which consisted of surgical treatments and endovascular treatments. Surgical treatments were open repair for vascular complications, and endovascular treatments mainly included angioplasty and stenting in the targeted vessel.

Risk-of-bias assessment
The risk of bias in non-randomized comparative studies was assessed using the Risk Of Bias In Non-randomized Studies -of Interventions (ROBINS-I) tool 13 by two authors (Y.X. and C.C.) independently. Bias due to confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, and selection of the reported result was assessed.

Statistical analysis
The data were analysed using R Studio (R version 4.1.1). Meta-analysis was performed using the Mantel-Haenszel method, and data were pooled using the random-effects model owing to the variability in each included study. The I 2 statistic was used to assess the heterogeneity among studies. Outcomes are reported as ORs with their 95 per cent confidence intervals. Publication and reporting biases were evaluated using Egger's test. Sensitivity analyses were further performed to confirm the stability of pooled results by excluding retrospective or small-sample studies. Studies with fewer than 500 patients were defined as small-sample studies in the current meta-analysis.

Study and population characteristics
The nine studies included three retrospective studies, five prospective studies, and one randomized trial. These studies were reported between 2015 and 2022, with sample sizes ranging from 191 to 2583. A total of 7529 patients were included for analysis, of which 4144 received ProGlide and 3385 received Prostar in transfemoral TAVR. The general characteristics of the included studies are shown in Table 1.
The mean age of the included patients was over 80 years and 54.8 per cent were female. Hypertension (81.5 per cent) was the most common combined disease in the pooled cohort, followed by diabetes mellitus (28.7 per cent); peripheral vascular disease (12.9 per cent) was less common. The baseline characteristics and cardiac operative risk stratification were comparable between the ProGlide group and the Prostar group ( Table S2).

Quality of the included studies
The risk of bias in the included studies was assessed using the ROBINS-I tool. In most of the included studies, the sheath sizes were similar between groups, but four studies 19,32,33,35 did not provide detailed information regarding sheath sizes, and were consequently considered to have a moderate risk of bias due to confounding ( Table 2). The bias due to selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, and selection of the reported result was deemed low in all included studies (Fig. S1).

Vascular complications
All included studies reported data regarding the outcomes of major and minor vascular complications in each group. The pooled data showed a significantly decreased risk of major vascular complications in the ProGlide group compared with the Prostar group, with an OR of 0.50 (95 per cent c.i. 0.32 to 0.78) (Fig. 2a). For minor vascular complications, no statistical significance was found between the ProGlide and Prostar groups, with an OR of 0.76 (95 per cent c.i. 0.53 to 1.10) (Fig. 2b).
The most common vascular complication was vascular trauma, occurring in 8.3 per cent of patients, with a similar risk in both groups (OR 0.95, 95 per cent c.i. 0.59 to 1.54) (Fig. 3a). Among all vascular trauma, no significant difference was found regarding dissection (OR 1. Records removed before screening: Duplicate records removed n = 81 Records identified from Embase, PubMed, and Cochrane library n = 734 Identification of studies via databases and registers      (Fig. S4). The outcome for bleeding complications was consistent after excluding small-sample    Berti 2020

Publication bias and sensitivity analyses
Heitzinger 2022 studies, but did not retain significant difference after the exclusion of retrospective studies. In addition, there was no significant difference in the risk of ischaemia complications between the two groups after the exclusion of retrospective or small-sample studies.

Discussion
The aim of the present study was to compare the vascular complications in large-bore arteriotomy closure with two suture-based VCDs: ProGlide and Prostar. To the best of the authors' knowledge, it is the first time the risks of different types of vascular complications have been pooled in a meta-analysis. The included TAVR studies adopted uniform evaluation systems, VARC-2 or VARC-3, to report vascular complications, so that it was possible to derive reliable results from the meta-analysis.
The main findings are that, compared with Prostar, ProGlide is a safer device with a decreased risk of major vascular complications; ProGlide has better procedural efficacy with lower risks of device failures and additional surgical treatments; and  ProGlide has a lower risk of bleeding complications, but a higher risk of ischaemia complications. For the outcome of major vascular complications, the majority of the included studies favoured ProGlide 7,[30][31][32][33]35 . The multicentre prospective study conducted by Barbash et al. 7 identified 472 patient pairs by propensity matching, making this study the only included study at low risk of bias. It provided reliable results, with a higher rate of major vascular complications in the Prostar group (7.4 versus 1.9 per cent (P < 0.001)). In addition, the recent study with the largest cohort also tended to favour ProGlide, with a propensity-adjusted OR of 0.85 (95 per cent c.i. 0.65 to 1.11) 34 . The studies by Barbanti et al. 8 and Marcusohn et al. 36 demonstrated higher incidences of major vascular complications in the ProGlide group (8.0 versus 3.9 per cent (P = 0.146) and 4.7 versus 3.8 per cent (P = 1.000) respectively). However, these results were non-significant, and both studies were single-centre retrospective studies with the smallest and second smallest sample size, which made the results relatively less reliable.
One potential reason for the lower incidence of major vascular complications in the ProGlide group was the lower device failure rate, which was also supported by the pooled evidence in the present study. It is assumed that the different failure rate was due to the different designs of these two devices. The Prostar device delivers four needles simultaneously through the arterial lumen, with any needle malposition leading to device failure. On the other hand, the ProGlide device delivers only two needles that are easier to manipulate, and two ProGlide devices are deployed independently, usually at the 10 and 2 o'clock positions. As a result, the risk of simultaneous failure of both ProGlide devices is low 9 . Insights from the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience reported 827 and 175 device failures of ProGlide and Prostar respectively. Only 12.7 per cent of the ProGlide failures were due to failed deployment, compared with 25.1 per cent for Prostar, indicating that it was easier for ProGlide to deploy successfully 20 .
In the current study, most of the included studies presented similar sheath sizes between groups, but, due to inadequate data, a subgroup analysis of sheath size could not be implemented. Based on recent studies, it is still uncertain whether the sheath size is associated with vascular complications. Some studies have reported that the sheath size is an independent predictor of major vascular complications 37,38 , whereas other studies have demonstrated that the difference in sheath diameter has no significant effect on the incidence of vascular complications 39,40 . Thus, RCTs are needed to provide further evidence.
The risk of different types of vascular complications of these two VCDs was first reported in a meta-analysis. The pooled results demonstrated that ProGlide was associated with fewer bleeding complications, but more ischaemia complications. Although the results were unstable in the sensitivity analyses, the potential trends were still clear. The reasons for these phenomena have rarely been discussed in previous studies and need further investigation. The fewer bleeding complications in the ProGlide group were potentially related to the lower device failure rate. For ischaemia complications, although the incidence was relatively low, there were more stenoses in the ProGlide group. Previous studies indicated that the interference of both sutures of independently deployed ProGlide may contribute to stenosis 36,41 . The manufacturer's recommended ProGlide deployment is to use two sutures at the 2 and 10 o'clock positions, creating an 'X'-shaped closure, which might cause suture entanglement and subsequent artery stenosis.
The present study found no significant difference in the risk of overall additional interventions, but the types of interventions varied between groups. Most vascular complications in the ProGlide group were treated using endovascular treatments, whereas surgical treatments were performed to deal with vascular complications in the Prostar group. This finding was similar to the report of post-marketing surveillance data from the FDA Manufacturer and User Facility Device Experience database 20 . The data showed that, although surgical interventions were commonly performed in both groups, 82.1 per cent of the adverse events in the Prostar group needed surgical repair, which was much higher than the 54.1 per cent of the ProGlide group. Additionally, 39.3 per cent of the adverse events in the ProGlide group could be treated with manual compression, but, in the Prostar group, it was only 5.3 per cent. One hypothesis was that when one of the ProGlide devices fails, the other one might still work because the two devices are deployed independently, which could limit the severity of events and reduce the need for surgical treatments.
There was one previous systematic review that compared ProGlide and Prostar in percutaneous transfemoral procedures, and no significant differences were observed in the rate of overall vascular complications 9 . This review was conducted in 2017, and only four TAVR studies were included for meta-analysis 7,8,31,42 . In comparison, the present meta-analysis incorporated five more studies published after 2017, including the study with the largest cohort 34 and the updated data from the population reported by Jochheim et al 42 . Thus, the present study demonstrated different results. In addition, the previous systematic review included a study on percutaneous endovascular aortic aneurysm repair (p-EVAR), but the p-EVAR study used an inconsistent definition of vascular complications with TAVR that increased the heterogeneity 27 . The results of the current study might be applicable to percutaneous thoracic endovascular aortic repair (TEVAR) and p-EVAR, which have a similar femoral artery procedure to TAVR.
This study also has some limitations. First, although most of the included studies are prospective studies, randomized trials are still rare, which limits the level of evidence. Second, due to inadequate data regarding sheath sizes, sheath to iliofemoral artery ratio, and arterial calcification in the included studies, the pooled results could not be adjusted according to these factors.
In percutaneous transfemoral TAVR procedures, ProGlide has superior safety and efficacy over Prostar, with lower risks of major vascular complications, device failures, and additional surgical treatments. In addition, ProGlide is related to fewer bleeding complications, but more ischaemia complications.